The pro-inflammatory effect of uraemia overrules the anti-atherogenic potential of immunization with oxidized LDL in apoE-/- mice.

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The pro-inflammatory effect of uraemia overrules the anti-atherogenic potential of immunization with oxidized LDL in apoE-/- mice.

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Publication Article, peer reviewed scientific
Title The pro-inflammatory effect of uraemia overrules the anti-atherogenic potential of immunization with oxidized LDL in apoE-/- mice.
Author(s) Pedersen, Tanja X ; Binder, Christoph J ; Nordin Fredrikson, Gunilla ; Nilsson, Jan ; Bro, Susanne ; Nielsen, Lars B
Date 2010
English abstract
BACKGROUND: Uraemia increases oxidative stress, plasma titres of antibodies recognizing oxidized low-density lipoprotein (oxLDL) and development of atherosclerosis. Immunization with oxLDL prevents classical, non-uraemic atherosclerosis. We have investigated whether immunization with oxLDL might also prevent uraemia-induced atherosclerosis in apolipoprotein E knockout (apoE-/-) mice. METHODS: ApoE-/- mice were immunized with either native LDL (n = 25), Cu(2+)-oxidized LDL (n = 25), PBS (n = 25), the apolipoprotein B-derived peptide P45 (apoB-peptide P45) conjugated to bovine serum albumin (BSA) (n = 25) or BSA (n = 25) prior to induction of uraemia by 5/6 nephrectomy (NX). RESULTS: Immunization with oxLDL increased plasma titres of immunoglobulin G (IgG) recognizing Cu(2+)-oxLDL and malondialdehyde-modified LDL (MDA-LDL). However, 5/6 NX induced a marked increase in plasma concentrations of anti-oxLDL antibodies as well as pro-atherogenic cytokines [interleukin (IL)-2 (IL-2), IL-4, IL-6 and IL-12)] in native mouse LDL (nLDL)-, oxLDL- and PBS-immunized mice. Even though nLDL- and oxLDL-immunized mice displayed higher anti-MDA-LDL IgG titres than the PBS group, aortic atherosclerosis lesion size was not affected by immunization. Immunization with the apoB-peptide P45, which consistently reduces classical atherosclerosis in non-uraemic mice, also did not reduce lesion size in uraemic apoE-/- mice. CONCLUSION: The results suggest that the pro-inflammatory and pro-atherogenic effect of uraemia overrules the anti-atherogenic potential of oxLDL immunization in apoE-/- mice.
DOI http://dx.doi.org/10.1093/ndt/gfq059 (link to publisher's fulltext)
Host/Issue Nephrology, dialysis, transplantation;8
Volume 25
ISSN 1460-2385
Pages 2486-2491
Language eng (iso)
Subject(s) Medicine
Research Subject Categories::MEDICINE
Handle http://hdl.handle.net/2043/11280 (link to this page)

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